MDMA and PTSD treatment: “PTSD: from novel pathophysiology to innovative therapeutics”

This article (2016) reviews the history and current state of MDMA as a potential treatment for PTSD.

Abstract

“There is a range of therapies to treat Post Traumatic Stress Disorder (PTSD) but treatment resistance remains high, with many sufferers experiencing the chronic condition. Engagement in trauma-focused psychotherapy is difficult for some patients with PTSD, especially those with extreme affect dysregulation associated with recall of traumatic memories. In recent years there have been a number of neuroscientific and clinical studies examining the potential role for adjunctive drug-assisted psychotherapy using 3,4,-methylenedioxmethamphetamine (MDMA) as a treatment for PTSD. re-visiting of a novel approach to trauma-focused psychotherapy with Used just two or three times, under careful medical supervision and specialised psychotherapy support MDMA appears to facilitate the recall of traumatic memories without the user feeling overwhelmed by the negative affect that usually accompanies such memories. This therapeutic approach began in the 1980s and was subsequently shelved in the midst of public health concerns surrounding the recreational use of the drug ecstasy. When pharmaceutical grade MDMA is used in a clinical setting it does not share the same risk profiles as ecstasy. Recent phase one neurophysiological studies and phase two clinical studies are showing promise as a potential new approach to managing treatment-resistant PTSD.”

Author: Ben Sessa

Summary

Over half of sufferers endure significant impairments in functioning, including struggling with relationships, parenting, financial, and self-medicating with illicit drugs or alcohol.

Multiple complex factors may affect treatment response in PTSD, but a drug that temporarily reduces apeutic relationship may be useful.

MDMA’s psychopharmacological profile makes it well suited as an adjunct for assisting trauma-focused psychotherapy. It reduces the sense of fear that accompanies the recall of traumatic memories, strengthens the therapeutic alliance and decreases avoidance behaviour. MDMA effects are due to the release of 5-hydroxytryptamine at 5-HT1A and 5-HT1B receptors, increased activity at 5-HT2A receptors, and a paradoxical sense of relaxation. MDMA improves levels of emotional arousal, improves fear extinction learning, improves feelings of trust and empathy, and puts the PTSD sufferer into the “opti- arousal zone” for psychotherapy, where they are appropriately and motivated to engage in the psychotherapeutic process, overly stimulated as to be hypervigilant and in a psychological state in which they are able address their traumatic memories.

MDMA-assisted psychotherapy sessions typically last eight to sixteen weeks, with three to six MDMA-assisted sessions spaced several weeks apart. The sessions are client-led and involve lying back with eyeshades on, little communication and long periods of non-verbal activity.

MDMA therapy involves receiving an initial dose of MDMA, followed by a second dose two hours later. Physical touch from the therapists is often employed as a therapeutic tool, with carefully managed professional boundaries, to allow the participant to externalise their psychological pain. MAPS has developed a treatment manual for trainee psychotherapists conducting MDMA-assisted psychotherapy studies, which includes a requirement that the therapist take MDMA under the supervision of trained MDMA Therapists.

The prefrontal cortex (PFC) is responsible for rationalising and overcoming the fear response, and the amygdala is required for accurate social judgments of others based on their facial expression.

Studies have shown that MDMA causes increased PFC activation and decreased amygdala activation in healthy controls and in response to observing angry faces. This effect is complemented by decreased connectivity between the prefrontal cortex and the amygdala and increased connectivity between the amygdala and hippocampus.

In the early 1980s, MDMA was administered to 29 patients as part of individual, group and couples therapy. The results were positive, and the method and experimental techniques that facilitate a successful drug-assisted session were described.

In 2010, psychiatrist Michael Mithoefer published the first randomised controlled study testing MDMA-assisted psychotherapy against placebo on 25 subjects with treatment-resistant PTSD. The results were sustained four years later, with 85% of the cohort remaining PTSD-free.

Patients with PTSD were randomized into MDMA-Assisted Psychotherapy or exposure therapy in combination with SSRI medication. MDMA-Assisted psychotherapy had larger effect sizes in terms of clinician-assessed outcomes and patient self-report outcomes.

Ecstasy has moderate abuse potential, but less so than other stimulants. There have been no deaths or serious adverse events in clinical MDMA studies, but there remains a negatively biased media depiction of ecstasy, which impairs medical research studies exploring potential MDMA treatments in psychiatry.

In 1992, a proposed study of MDMA-assisted psychotherapy for treating anxiety secondary to end-stage cancer was switched from MDMA to psilocybin after being twice rejected by the FDA. Impediments to MDMA research include difficulties accessing quality (GMP) MDMA and obtaining the necessary expensive time-consuming Schedule One licenses.

Phase Two MDMA-PTSD studies are nearing completion, with an RCT on post-combat veterans from the Iraq and Afghanistan wars. Phase Three studies are planned across multiple international sites from 2018.

MDMA and other psychedelic drugs could hold significant potential as adjuncts to traditional treatment models, including PTSD, post-detox alcoholics and understanding the neurobiology of higher order socioemotional states such as empathy and trust.